BIOLOGIC BEHAVIOUR


General Considerations

•apocrine gland anal sac ADC accounts for 2% of all skin tumors

•anal sac ADC is more common in dogs and very rare in cats

•other anal sac tumors include adenoma and SCC

•metastasis and hypercalcemia is rare in cats with anal sac ADC

•site: firm and fixed mass with local invasion at either 4 o'clock or 8 o'clock

•anal sac mass may be small and hypercalcemia or metastasis may be detected prior to anal sac mass


Paraneoplastic Hypercalcemia

•paraneoplastic hypercalcemia is common and present in 27%-90% cases

•hypercalcemia is associated either with the anal sac ADC or, more commonly, with regional lymph node metastasis

•hypercalcemia of malignancy or pseudohyperparathyroidism is due to the production of PTH-related protein which is consistently and markedly increased compared to normal dogs and decreases to normal range following surgical resection

•linear relationship between total serum calcium and PTH-related protein in dogs with anal sac ADC

•parathyroid glands are atrophied in dogs with anal sac ADC and hypercalcemia

•complete or near complete removal of tumor burden will often reverse hypercalcemia within 1-2 days

•recurrence of hypercalcemia is indicative of local tumor recurrence or metastasis


Metastasis

•56%-79% metastatic rate at the time of diagnosis with regional lymph node very common (47%-72%)

•metastatic sites: regional lymph nodes (sublumbar), lungs, spleen, bone (appendicular and axial skeleton), pancreas, heart, and mediastinum



CLINICAL FEATURES


Signalment

•breed predisposition: GSD, English Cocker Spaniel, Dachshund, Alaskan Malamute, and English Springer Spaniel

•median age 10-11 years

•sex predilection for spayed female was initially reported, but majority of studies do not support this finding


Clinical Signs

•perianal mass or incidental finding

•clinical signs usually caused by either hypercalcemia (i.e., polyuria, polydipsia, and urinary incontinence) or obstruction of pelvic canal secondary to metastatic lymphadenopathy (i.e., constipation and tenesmus)

•pain, lameness ± neurologic disease occasionally seen due to regional bone metastasis ± direct extension from sublumbar lymph nodes to lumbar vertebra


Diagnosis

•rectal examination to assess sublumbar lymph node size and mobility

•serum biochemistry: ionized calcium and renal profile

•FNA of anal sac mass may differentiate perianal tumors from other tumor types but will rarely differentiate benign from malignant perianal tumors (benign anal sac tumors are very rare)

•caudal abdominal radiographs or, preferably, ultrasound, CT, or MRI to assess sublumbar lymph node size

•FNA of sublumbar lymph node may differentiate metastatic lymph node from other causes of lymphadenomegaly

•chest radiographs: pulmonary metastasis is uncommon without sublumbar lymph node metastasis



TREATMENT


Surgery

•aggressive saline diuresis ± diuretic therapy may be required prior to surgery if hypercalcemic with renal failure

•wide local resection:

•resection of < 50% of anal sphincter will cause transient but not permanent fecal incontinence

•complete resection often difficult due to proximity to rectum and poor definition of perianal area

•recurrent disease difficult to resect

•exploratory celiotomy and sublumbar lymphadenectomy:

•sublumbar lymph nodes can be resected in approximately 50% of cases

•resectability cannot be determined preoperatively and large sublumbar nodes do not preclude resection

•sublumbar lymph nodes can either be invasive or easily removed

•castration has no benefit

•omentalization of the sublumbar lymph nodes has been described in 1 dog for palliation of tenesmus and dysuria caused by metastatic cystic sublumbar lymph nodes

•10% complication rate associated with anal sac resection including intraoperative hemorrhage, infection, fecal or urinary incontinence, hypocalcemia, tenesmus, and perianal fistula formation


Radiation Therapy

•indications: inoperable anal sac ADC and metastatic ± inoperable sublumbar lymph node

•radiation therapy can be used either intraoperative (10-15 Gy) for treatment of the sublumbar lymph nodes or postoperative for both the anal sac ADC and sublumbar lymph nodes


Chemotherapy

•effect of chemotherapy is unknown

•platinum drugs have shown 30%-33% PR in 2 studies

•doxorubicin ± cyclophosphamide has been associated with short-term PR

•mitoxantrone has been combined with radiation therapy

•piroxicam has no proven effect but antitumor and antiangiogenic effects may be beneficial


Prognosis

•fair to good prognosis

•anal sacculectomy ± radiation therapy provides good control of local disease

•however, anal sacculectomy alone will often result in failure at sublumbar lymph nodes

•surgery ± intraoperative ± adjunctive radiation therapy may be effective for control of sublumbar lymph nodes and is associated with mild to marked colitis and proctitis

•local tumor recurrence in 45%-50% with a median DFI 10 months

•MST 544 days, with 2-year survival rate 37%

•MST 500 days for surgery alone, with 1-year survival rate 65% and 2-year survival rate 29%

•MST 657 days for radiation therapy alone, with 1-year survival rate 79% and 2-year survival rate 38%

•MST 540 days for surgery and chemotherapy, with 1-year survival rate 69% and 2-year survival rate 36%

•MST 742-956 days for surgery, radiation therapy, and chemotherapy, with 1-year survival rate 80%, 2-year survival rate 56%, and 3-year survival rate 35%

•poor prognostic signs include lung ± lymph node metastasis, hypercalcemia, tumor size, and treatment, with MST significantly shorter with:

•lung metastasis (219 days v 584 days) ± any metastasis (16 months v 6 months)

•hypercalcemia (256 days v 584 days)

•tumors ≥ 10 cm 2 (292 days v 584 days)

•dogs not treated with surgery (402 days v 548 days)

•dogs treated with chemotherapy alone (212 days v 584 days)

•no significant difference in survival for dogs with surgically resected sublumbar lymph nodes and dogs without sublumbar lymph node metastasis

•cause of death renal failure secondary to hypercalcemia or local or distant metastasis

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APOCRINE GLAND ANAL SAC ADENOCARCINOMA

● Surgical Oncology JournalsJournals.html
● Surgical Oncology SocietiesSocieties.html
● Veterinary Surgery CollegesColleges.html

Interpretation

Cortisol Level

Normal

250-450 nmol/L

Pituitary- or adrenal-dependent hyperadrenocorticism

> 600 nmol/L

Iatrogenic hyperadrenocorticism

< 150 nmol/L

Interpretation

3 Hours

Normal

< 40 nmol/L

Pituitary-dependent hyperadrenocorticism

< 40 nmol/L

Pituitary- or adrenal-dependent hyperadrenocorticism

> 40 nmol/L

8 Hours

< 40 nmol/L

> 40 nmol/L

> 40 nmol/L

Diagnostic Test

Sensitivity

Specificity

Accuracy

LDDST

85%-100%

44%-73%

58%-92%

ACTH Stimulation

80%-95%

82%-91%

84%-93%

Urine Cortisol-to-Creatinine

50%-100%

22%-100%

37%-91%

Interpretation

Cortisol Level

Pituitary-dependent hyperadrenocorticism

< 50% T0 cortisol concentration

Pituitary- or adrenal-dependent hyperadrenocorticism

> 50% T 0 cortisol concentration

Interpretation

Cortisol Level

Normal

37-80 ng/L

Pituitary-dependent hyperadrenocorticism

> 75 ng/L

Adrenal-dependent hyperadrenocorticism

< 37 ng/L